VSG GENE-CONTROL AND INFECTIVITY STRATEGY OF METACYCLIC STAGE TRYPANOSOMA-BRUCEI

As the metacyclic trypanosome stage develops in the tsetse fly salivar y glands, it initiates expression of variant surface glycoproteins (VS Gs) and does so by each cell activating, at random, one From a small s ubset of metacyclic VSG (M-VSG) genes. Whereas differential activation of individual VSG genes in the bloodstream occurs as a function of ti me, to evade waves of antibody, it is believed that the aim in the met acyclic stage is simultaneously to generate population diversity. M-VS G genes are activated in their telomeric loci and belong to monocistro nic transcription units, unlike all other known trypanosome protein-co ding genes, which appear to be transcribed polycistronically. The prom oters of these metacyclic expression sites (M-ESs) have the unique pro perty. in this organism, of being switched on and off in a life-cycle stage specific pattern. We have found that the 1.22 M-ES promoter is r egulated according to life cycle stage, differential control bring exe rted through different elements of the promoter and under the influenc e of its genomic locus. We have characterized in detail the telomeres containing the 1.22 and 1.61 M-ESs. Upstream of the M-ES is a possibly haploid, non-transcribed region with some degenerate sequences homolo gous with expression site associated genes (ESAGs) that occur in blood stream VSG expression sites. Further upstream (respectively, 22 and 13 kb upstream of the 1.22 and 1.61 VSG genes) are alpha-amanitin sensit ive transcription units that may be polycistrons and are transcribed i n all examined life cycle stages. They contain a number of genes. The differences between metacyclic and bloodstream ESs may have important consequences for life cycle regulation, genetic stability, phenotype c omplexity and adaptability of the metacyclic stage as it infects diffe rent host species. (C) 1998 Francqui Foundation. Published by Elsevier Science B.V. All rights reserved.